Diagnostic device

ABSTRACT

Diagnostic agent for the detection of components contained in liquids, e.g. body fluids, comprising a felt or fleece of preponderantly polyamide fibers and impregnated with appropriate reagents.

United States Patent Lange et a1.

[451 July 29, 1975 DIAGNOSTIC DEVICE Inventors: Hans Lange, Lampertheim;Walter Rittersdorf; Hans-Georg Rey, both of Mannheim-Waldhof, all ofGermany Assignee: Boehringer Mannheim GmbH,

Mannheim, Germany Filed: Nov. 13, 1972 Appl. No.: 306,127

Foreign Application Priority Data Nov. 24, 1971 Germany 2158124References Cited UNITED STATES PATENTS 7/1963 Free 23/253 TP Mast 23/253TP Rey et a1 23/253 TP OTHER PUBLICATIONS Edelman G. M., Rutishauser U.,and Millette C. F.; Cell Fractionation and Arrangement on Fibers, Beadsand Surfaces; Proc. Nat. Acad. Sci. USA. Vol. 68, No. 9, pp. 2153-2157,September 1971.

Primary Examiner.1oseph Scovronek Assistant Examiner-Dale LovercheckAttorney, Agent, or Firm-Burgess, Dinklage & Sprung Diagnostic agent forthe detection of components contained in liquids, e.g. body fluids,comprising a felt or fleece of preponderantly polyamide fibers andimpregnated with appropriate reagents.

ABSTRACT 17 Claims, No Drawings DIAGNOSTIC DEVICE The present inventionis concerned with diagnostic agents for the detection of components inliquids, especially in body fluids, comprising an absorbent carrierimpregnated with reagents.

Test strips impregnated with suitable reagents have been in use for along time for detecting components of liquids. pH indicator papers areused very widely but other reagent papers are also employed. In recentyears, test papers have achieved great importance for the detection ofglucose, protein, nitrite and the like in body fluids, for example inurine and blood, because they enable the physician to carry out a rapidand simple diagnosis of metabolic disturbances outside the laboratory.

For the various tests, a large number of absorbent carriers has beenproposed, for example, wood, asbestos, gypsum, glass fiber felts,synthetic resin fleeces and the like, but in actual practice filterpaper is used almost exclusively for the commercially available teststrips. The reason for this is that, in addition to the cheapness andease of working up of paper, the reagents on the cellulose fibers of thepaper are especially reactive.

Although filter paper is usually the best carrier material, there arechemical test reactions which cannot be carried out on paper. Quiteapart from test reagents which, in a state of fine division, areunstable in air and, therefore, cannot be applied to a carrier byimpregnation, there are a number of test reagents which destroy paperfibers and make the paper brittle. Such reagents include, for example,strongly alkaline, strongly acidic and oxidizing substances andespecially reagent mixtures with a high salt content.

Tests which are especially important for medical diagnosis but whichcannot be carried out or cannot be carried out satisfactorily with theuse of test strips include, for example, Legals test for ketonic bodiesand Ehrlichs test of pyrrole bodies. Legals test requires, for asatisfactory functioning, a high concentration of a strongly alkalinebuffer in the reaction solution and Ehrlichs test requires a highconcentration of a weakly acidic compound, for example, oxalic acid orpotassium bisulfate.

Filter papers which have been impregnated with the high saltconcentrations necessary for these test admittedly show a rapid andsensitive reaction with the substrates in question but are so hard andbrittle that they cannot be bent, folded or cut up without breaking andcrumbling. Since not only in the production but also in the transportand use of such strips, mechanical stresses constantly occur, theusefulness of such strips is severely limited.

Attempts to make such papers mechanically more stable by laminating onto a synthetic resin film were unsuccessful because the hard paper, uponbending or folding, again separated or crumbled away from the film.Cellulose fleece strengthened with synthetic resin fibers, for example,with polyvinyl chloride or polyester fibers, also have not proved to beadvantageous because they still did not possess a sufficient degree ofstability.

The obvious complete replacement of cellulose by more stabel syntheticresin fibers, for example by polypropylene fibers, such as has beenpropsed in German Patent Specification No. 2,007,013 for a bilirubintest,

also do not prove to be successful in the case of the above mentionedtests since these test strips show a sufficient mechanical stability butonly showed very weak color changes which, in the lower concentrationranges, could no longer be evaluated as an indication of bilirubin.

Microscopic investigations have shown that the important differencebetween the cellulose fibers of paper and synthetic resin fibers is thatthe cellulose fibers swell during the impregnation and a part of thereagents is embedded or incorporated into the fibers, whereas in thecase of synthetic resin fibers, the reagents are only deposited on thesurfaces of the fibers.

After laborious and fruitless experiments with a very large variety ofabsorbent materials, especially with various synthetic resin fleeces, wehave now, surprisingly, found, that the felts or fleeces of the instantinvention differ significantly from all of the other materials tested.

The present invention provides diagnostic agents comprising an absorbentcarrier which consists entirely or preponderantly of polyamides. Onlythese fleeces or felts based on polyamides provide the final test stripswith a sufficient degree of stability, without destroying the reactivityand sensitivity of the test reagents.

It is not known why polyamides differ in this manner from othersynthetic resins, for example from polyesters and polyvinyl chlorides.The difference is extremely surprising because the reagents are also notembedded or incorporated into the polyamide fibers.

As polyamides to be used according to the present invention, there canbe employed not only those of the nylon type, made from dicarboxylicacids and diamines, but also those of the perlon type, made fromw-aminocarboxylic acids. As mixture components in mixed felts andfleeces, it is especially preferred to use polyester fibers but fibersof other synthetic resins, for example of polyvinyl chloride and thelike, can also be admixed in amounts of up to 50%.

The felts and fleeces can be produced not only be wet-depositing butalso by dry-depositing, the fibers can be oriented or lie at random andthey can be connected thermally or by binding agents or they can beneedled.

The felt or fleece selecteddepends essentially upon the nature of thereagents to be used for the impregnation thereof. From the large numberof commercially available felts and fleeces the best one can easily bedetermined by a few simple preliminary experiments.

Thus, in the case of impregnation with acidic salts, for example withpotassium bisulfate in the case of the urobilinogen test, it isrecommended to use a mixed felt or fleece containing polyester fibers.On the other hand, in the case of basic salts, such as are used for theketonic body test, pure polyamide felt or fleece has proved to be thebest. In special cases, a mixed felt 0r fleece of polyamide fibers andcellulose fibers can also be used.

The thickness and weight per unit area of the felt or fleece used can bevaried. However, very thin or light felts and fleeces take up verylittle reagent and thus have a poorer reactivity. Thick or voluminousfelts and fleeces, on the other hand, take up large amounts of reagentsand it is thus more difficult to work them up. Here again, the mostsuitable felt or fleece for any particular case can be easily determinedby a few simple preliminary experiments.

-polyvinylpyrrolidone-vinyl acetate surface-active agent solution Thefelt or fleece can be impregnated in conventional manner. However, inorder to improve wettability, it is sometimes desirable either to add awetting agent to the impregnation solution or first to impregnate thefelt or fleece with a wetting agent.

The impregnated felt or fleece is then dried in the usual manner. Ifdesired, it can be cut up into narrow strips and used directly or, asstill smaller pieces, can either be stuck on to a handle of syntheticresin or, according to German Patent Specification No. 1,546,307, can besealed between synthetic resin films or, according to German PatentSpecification No. P 21 18 455.4, can be sealed between a synthetic resinfilm and a synthetic resin mesh.

The following Examples are given for the purpose of illustrating thepresent invention, the properties of the fleeces and felts used in thefollowing Examples being summarized in Table 4 given hereinafter.

EXAMPLE 1 Urobilinogen Test The materials set out in the following Tablel were impregnated with an aqueous solution containing, per 100 ml, 20 gpotassium bisulfate and 0.2 g pdimethylaminobenzaldehyde. The propertiesof the impregnated test strips, as well as their reactions withurobilinogen-containing urine, were also set out in the following Table1.

The material numbers are described in Table 4, infra.

EXAMPLE 2.

Ketonic Body Test The materials set out in the following Table 2 wereimpregnated with Solution I, dried, impregnated with Solution II andagain dried.

Solution l trisodium phosphate dodecahydrate disodium hydrogen phosphatedihydrate glycocoll distilled water Solution ll sodium nitroferricyanidedihydrate copolymer (50% solution in ethanol) organic phosphate ester ofanionic 38.0 ml 18.5 ml ad 100.0 ml

The properties of the impregnated test strips and the reactions withurine containing increasing amounts of acetoacetate or of acetone werealso set out in the following Table 2.

TABLE 2 material and stability reaction material number filter paper (1)very brittle very good uniform polyester fleece (9) stable weaknon-unifonn polyamide fleece (5) stable good uniform EXAMPLE 3 KetoneBody Test The materials set out in the following Table 3 wereimpregnated with Solution I, dried, again impregnated with Solution IIand again dried.

Solution 1 tetrasodium ethylenediaminetetraacetate 38.5 g glycocoll 18.7g distilled water ad 100.0 ml Solution ll sodium nitroferricyanidedihydrate 1.0 g dimethyl formamide 40.0 ml methanol ad 100.0 ml

The following Table 3 also shows the mechanical properties and thereactions of the test strips with urine which contains increasingamounts of acetoacetate or of acetone.

polyester fleece l0) The following Table 4 gives the properties anddescription of the various carrier materials used in the above Examples:

TABLE 4 material material type producer synthetic working up thicknesswt. per No. (in Western resin monin mm. unit Germany) omers and area inaverage g/m mol. wt.

1 filter paper 23SL Schleicher random, with 0.45 230 8!. Schull wet tearstrength agent 2 cellulose- Paratex Lohmann longitudinally 0.2 190cottonwool Ill/50 KG laid with fleece (7:3) binding agent 3 regeneratedVS 446 Binzer vinyl random, with 0.5 100 cellulosechloride binding agentpolyvinyl M.W. about chloride 100,000 fleece (95:5) 4 regenerated(sample) Binzer c-caprorandom, with 1.0 150 celluloselactam bindingagent polyamide M.W. about fleece (1:1) 22,000 5 polyamide V 27835 C.Freue-caprolongitudinally 0.35 l00 fleece (sample) denberg lactam andtransverse- M.W. about ly laid, therm- 20,000 ally strengthened 6polyamide N 933C C. Freu e-caprolongitudinally 0.5 95

fleece (sample) denberg lactam and transverse- M.W. about ly laid,therm- 20,000 ally strengthened 7 polyamide FT 21 14 C.Freue-caprolongitudinally 0.25 80 fleece denberg lactam and transverselyM.W. about laid, thermally 20,000 strengthened 8 polyester- SuprotexKalle terephthalic longitudinally 1.5 300 polyamide acid-ethylene andtransversely fleece glycol M.W. laid, thermally (1:1) about 18,000strengthened,

adipic acidneedled, without hexamethylenebinding agent diamine, M.W.about 20,000 9 polyester E 5209 Kalle terephthalic needled, therm- 0.35250 fleece (sample) acid-ethylene ally strengthened glycol M.Wv about18,000 10 polyester H 1015 C. Freuterephthalic longitudinally 0.25 170fleece denberg acid-ethylene and transversely glycol M.W. laid,thermally about l8,000 strengthened It will be understood that thespecification and examples are illustrative but not limitative of thepresent invention and that other embodiments within the spirit and scopeof the invention will suggest themselves to those skilled in the art.

We claim:

1. Diagnostic device for the detection of components contained inliquids, which diagnostic device comprises an absorbent carriercomprising felt or fleece preponderantly consisting of polyamide fibers,wherein said carrier is impregnated with appropriate reagents.

2. Diagnostic device as claimed in claim 1 wherein said absorbentcarrier contains up to 50 percent by weight of fibers other thanpolyamide fibers.

3. Diagnostic device as claimed in claim 2 wherein said other fiber isat least one member of the group consisting of polyester fibers,polyvinylchloride fibers and cellulose fibers.

4. Diagnostic device as claimed in claim 1 in which the felt or fleecefibers are oriented directionally.

5. Diagnostic device as claimed in claim 1 in which the felt or fleecefibers are randomly disposed.

6. Diagnostic device as claimed in claim 1 wherein the fibers of thefelt or fleece are bonded thermally or by means of bonding agents.

7. Diagnostic device as claimed in claim 1 wherein said felt or fleeceis a needled felt or fleece.

8. Diagnostic device as claimed in claim 1 wherein said carrier isimpregnated with a wetting agent.

9. Diagnostic device as claimed in claim 1 wherein the reagents arestrongly alkaline phosphate buffer, sodium nitroferricyanide andglycocoll, for carrying out Legals test for ketonic bodies.

10. Diagnostic device as claimed in claim 1 wherein the reagents arepotassium bisulfate and pdimethylaminobenzaldehyde, for carrying outEhrlichs test for urobilinogen.

11. Diagnostic device as claimed in claim 1 wherein said absorbentcomposition is in the form of a narrow strip adhered to a syntheticresin backing extending therefrom.

12. Diagnostic device as claimed in claim 1 wherein said absorbentcarrier is sealed between two synthetic resin films.

13. Diagnostic device as claimed in claim 1 wherein said absorbentcarrier is sealed between a synthetic resin film and a synthetic resinmesh.

14. Diagnostic device as claimed in claim 9 wherein said absorbentcarrier consists essentially of pure polyamide felt or fleece.

15. Diagnostic device as claimed in claim 10 wherein said absorbentcarrier is a mixed felt or fleece also containing polyester fibers.

16. Diagnostic device as claimed in claim 1 wherein the polyamide is ofthe nylon type.

17. Diagnostic device as claimed in claim 1 wherein the polyamide is ofthe perlon type.

1. DIAGNOSTIC DEVICE FOR THE DETECTION OF COMPONENTS CONTAINED INLIQUIDS, WHICH DIAGNOSTIC DEVICE COMPRISES AN ABSRBENT CARRIERCOMPRISING FELT OR FLEECE PREPONDERANTLY CONSISTING OF POLYAMIDE FIBERS,WHEREIN SAID CARRIER IS IMPREGNATED WITH APPROPRIATE REGENTS. 2.Diagnostic device as claimed in claim 1 wherein said absorbent carriercontains up to 50 percent by weight of fibers other than polyamidefibers.
 3. Diagnostic device as claimed in claim 2 wherein said otherfiber is at least one member of the group consisting of polyesterfibers, polyvinylchloride fibers and cellulose fibers.
 4. Diagnosticdevice as claimed in claim 1 in which the felt or fleece fibers areoriented directionally.
 5. Diagnostic device as claimed in claim 1 inwhich the felt or fleece fibers are randomly disposed.
 6. Diagnosticdevice as claimed in claim 1 wherein the fibers of the felt or fleeceare bonded thermally or by means of bonding agenTs.
 7. Diagnostic deviceas claimed in claim 1 wherein said felt or fleece is a needled felt orfleece.
 8. Diagnostic device as claimed in claim 1 wherein said carrieris impregnated with a wetting agent.
 9. Diagnostic device as claimed inclaim 1 wherein the reagents are strongly alkaline phosphate buffer,sodium nitroferricyanide and glycocoll, for carrying out Legal''s testfor ketonic bodies.
 10. Diagnostic device as claimed in claim 1 whereinthe reagents are potassium bisulfate and p-dimethylaminobenzaldehyde,for carrying out Ehrlich''s test for urobilinogen.
 11. Diagnostic deviceas claimed in claim 1 wherein said absorbent composition is in the formof a narrow strip adhered to a synthetic resin backing extendingtherefrom.
 12. Diagnostic device as claimed in claim 1 wherein saidabsorbent carrier is sealed between two synthetic resin films. 13.Diagnostic device as claimed in claim 1 wherein said absorbent carrieris sealed between a synthetic resin film and a synthetic resin mesh. 14.Diagnostic device as claimed in claim 9 wherein said absorbent carrierconsists essentially of pure polyamide felt or fleece.
 15. Diagnosticdevice as claimed in claim 10 wherein said absorbent carrier is a mixedfelt or fleece also containing polyester fibers.
 16. Diagnostic deviceas claimed in claim 1 wherein the polyamide is of the nylon type. 17.Diagnostic device as claimed in claim 1 wherein the polyamide is of theperlon type.